Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L

Aim To explore the role of cotranscriptional activator p300 in regulating the electrical remodeling of atrial myocytes in aging mouse, which resulted in atrial fibrillation. Methods The left atrial appendage tissues of 5 , 13 and 18monthold C57BL/6 mice were collected respectively. Western blot was used to detect the protein expression levels of p300, L type calcium channel (Cavl. 2) and aging related protein p53/p21. Acute enzymatic hydrolysis was used to isolate single atrial myocytes, and the wholecell patchclamp technique was used to detect the Ltype calcium current (I

Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 μmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.
Animals ; Down-Regulation ; Heart Atria ; Myocytes, Cardiac ; Rats ; Tumor Necrosis Factor-alpha ; src-Family Kinases

This project is to investigate lignans from the dried fruits of Xanthium sibiricum (Xanthii Fructus). The chemical constituents were extract by 70% ethanol and isolated by silica gel, ODS, Sephadex LH-20, MCI column chromatography. Based on comparison of their spectral data with those reported in literature, they were elucidated as (-)-pinoresinol (1), balanophonin A (2), diospyrosin (3), dehydrodiconiferyl alcohol (4), 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol (5), (-)-simulanol (6), (-)-7R,8S-dehydrodiconiferyl alcohol (7), chushizisin E (8), dihydrodehydrodiconiferyl alcohol (9), 7R,8S-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (10), erythro-1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (11), leptolepisol D (12), 8-O-4' neolignan 4-O-β-glucopyranoside (13), (-)-1-O-β-D-glucopyranosyl-2-{2-methoxy-4-[1-(E)-propen-3-ol]phenoxyl}-propane-3-ol(14), 1-(4-hydroxy-3-methoxy)-phenyl-2-[4-(1,2,3-trihydroxypropyl)-2-methoxy]-phenoxy-1,3-propandiol (15), threo-dihydroxy dehydrodiconiferyl alcohol (16), (-)-(2R)-1-O-β-D-glucopyranosyl-2-{2-methoxy-4-[(E)-formylviny1]phenoxyl} propane-3-ol (17). Compound 2-17 were isolated from the genus Xanthium for the first time. Compound 1 were isolated form Xanthii Fructus for the first time.

There is no doubt that the traditional Chinese medicine(TCM) is effective, practical and scientific after it was used for thousands of years. However, the mechanisms of action of many TCM are still unclear because of their multi-component, multi-target and multi-level features, which hinder the modernization and internationalization of the TCM. Proteomics is to analyze the composition and activity of intracellular proteins which are changing dynamically from a holistic perspective. It is consistent with the holistic and dynamic views of the TCM and brings about the hope of clarifying the mechanism of action of the TCM. In recent years, great progress has been made in the application of proteomics to determine the mechanism of the TCM. This article introduced the core technologies of proteomics and systematically summarized the applications of proteomics in the study of the mechanism of the Chinese medicinal formulae, single Chinese medicine and monomeric compounds from the TCM to provide innovative ideas and methods for reference.

The genus Ephedra of the Ephedraceae family contains more than 60 species of nonflowering seed plants distributed throughout Asia, America, Europe, and North Africa. These Ephedra species have medicinal, ecological, and economic value. This review aims to summarize the chemical constituents and pharmacological activities of the Ephedra species to unveil opportunities for future research. Comprehensive information on the Ephedra species was collected by electronic search (e.g., GoogleScholar, Pubmed, SciFinder, and Web of Science) and phytochemical books. The chemical compounds isolated from the Ephedra species include alkaloids, flavonoids, tannins, polysaccharides, and others. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Ephedra species showed anti-inflammatory, anticancer, antibacterial, antioxidant, hepatoprotective, anti-obesity, antiviral, and diuretic activities. After chemical and pharmacological profiling, current research is focused on the antibacterial and antifungal effects of the phenolic acid compounds, the immunosuppressive activity of the polysaccharides, and the antitumor activity of flavonoids.
Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Antioxidants ; chemistry ; pharmacology ; Antiviral Agents ; chemistry ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Ephedra ; chemistry ; Humans

Backcground:Ankyrin repeat and SOCS box protein 3 (ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain.Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses.However,its effects on oncogenesis are unclear.This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer (CRC).Methods:We used next-generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines,and used real-time quantitative polymerase chain reaction,Western blotting,and immunohistochemical or immunofluorescence assay to determine gene expression.We evaluated cell proliferation by MTT and colony formation assays,tested cell cycle distribution by flow cytometry,and assessed cell migration and invasion by transwell and wound healing assays.We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results:We found that ASB3 gene was frequently mutated (5.3％) and down-regulated (70.4％) in CRC cases.Knockdown of endogenous ASB3 expression promoted CRC cell proliferation,migration,and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo.Conversely,the ectopic overexpression of wild-type ASB3,but not that of ASB3 mutants that occurred in clinical CRC tissues,inhibited tumor growth and metastasis.Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial-mesenchymal transition,which was characterized by the up-regulation of β-catenin and E-cadherin and the down-regulation of transcription factor 8,N-cadherin,and vimentin.Conclusion:ASB3 dysfunction resulted from gene mutations or down-regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

Adult ; Dimethylformamide ; poisoning ; Female ; Humans ; Occupational Exposure ; Young Adult

OBJECTIVETo investigate the clinical manifestation of patients with renal injury induced by chronic mercury intoxication and the application of the diagnostic criteria of occupational mercury poisoning.

METHODSThe clinical data of 8 patients with chronic occupational mercury intoxication were analysed and evaluated.

RESULTSAll the observed clinical signs of chronic mercury intoxication correspond with the items of the diagnostic criteria of occupational mercury poisoning. The increasing beta2-MG was one of the clinical manifestations of renal injury induced by chronical mercury intoxication. The renal injury obviously was dose-dependent and reversible.

CONCLUSIONSThe national diagnostic criteria of occupational mercury poisoning is practically valuable. The renal injury induced by chronic mercury intoxication should not be neglected.

Adult ; Female ; Humans ; Male ; Mercury Poisoning ; diagnosis ; Middle Aged ; Occupational Diseases ; diagnosis ; Reference Standards

Objective To describe the prevalence and risk factors for suicide ideation among college students in Chongqing city. Methods Data on suicide ideation and related factors were collected from 9808 college students at 11 colleges randomly selected in Chongqing. A multiple logistic regression model was used to identify risk factors for suicide ideation. Results 1279 (13.0%) of the 9808 students reported suicide ideation and the constituent ratio of boys and girls was 3:4 whileriskfactors for suicide ideation were ranked as follows: high frequency of feeling hopeless in prior year (OR=5.07,95%CI: 4.27-6.02); having psychological problems in recent 1 month that affecting daily lives and learning(2.07,1.79-2.38); relatives having suicide behavior (1.77,1.52-2.08); having had sexual experience (1.95,1.65-2.30); being female (1.66,1.45-1.90) and friends who had had suicide attempts(1.46,1.28-1.67);having diseases in the last 1 month that affecting daily lives and learning (1.29,1.08-1.52). Conclusion The prevalence of suicide ideation among these college students was high that calls the development,implementation and assessment of suicide prevention plans for college students that focusing on the risk factors identified for suicide ideation.